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First published online May 30, 2007
doi: 10.1242/10.1242/dev.02855

Development 134, 2303-2314 (2007)
Published by The Company of Biologists 2007
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EEL-1, a Hect E3 ubiquitin ligase, controls asymmetry and persistence of the SKN-1 transcription factor in the early C. elegans embryo

Barbara D. Page1,2,3,*, Scott J. Diede4, Jennifer R. Tenlen1,5 and Edwin L. Ferguson3,6

1 Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
2 Howard Hughes Medical Institute, Seattle, WA 98109, USA.
3 Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
4 Children's Hospital and Regional Medical Center, Department of Hematology and Oncology, Seattle, WA 98105, USA.
5 Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
6 Committee on Developmental Biology, University of Chicago, Chicago, IL 60637, USA.

* Author for correspondence (e-mail: bdpage{at}gmail.com)

Accepted 22 March 2007

During early divisions of the C. elegans embryo, many maternally supplied determinants accumulate asymmetrically, and this asymmetry is crucial for proper cell fate specification. SKN-1, a transcription factor whose message is maternally supplied to the embryo, specifies the mesendodermal cell fate. In the 2-cell embryo, SKN-1 is expressed at a higher level in the posterior cell. This asymmetry becomes more pronounced at the 4-cell stage, when SKN-1 is high in the posterior cell's daughters and low in the daughters of the anterior blastomere. To date, the direct mechanisms that control SKN-1 distribution remain unknown. In this report, we identify eel-1, which encodes a putative Hect E3 ubiquitin ligase that shares several domains of similarity to the mammalian E3 ligase Mule. EEL-1 binds SKN-1 and appears to target SKN-1 for degradation. EEL-1 has two functions in regulating SKN-1 during early embryogenesis. First, eel-1 promotes the spatial asymmetry of SKN-1 accumulation at the 2- and 4-cell stages. Second, eel-1 acts in all cells to downregulate SKN-1 from the 12- to the 28-cell stage. Although loss of eel-1 alone causes a reduction in SKN-1 asymmetry at the 2-cell stage, the function of eel-1 in both the spatial and temporal regulation of SKN-1 is redundant with the activities of other genes. These data strongly suggest that multiple, functionally redundant pathways cooperate to ensure precise control of SKN-1 asymmetry and persistence in the early embryo.

Key words: SKN-1, Hect ubiquitin ligase, Protein degradation, Cell fate specification, Asymmetric cell division






© The Company of Biologists Ltd 2007